Characterization of HER2‐low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study

Background Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)‐low‐expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. Methods Women aged ≤40 years with newly diagnosed early‐stage HER2‐negative BC (HER2‐0 and HER2‐low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi‐square test and Student t‐test were used to describe variable distribution between HER2‐0 and HER2‐low. Associations with HER2‐low status were assessed with logistic regression. Kaplan–Meier method and Cox regression analysis were used to assess disease‐free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. Results Of 3547 included patients, 32.3% had HER2‐low BC, representing 46.3% of hormone receptor–positive and 21.3% of triple‐negative (TN) tumors. HER2‐low vs. HER2‐0 BC were more often of grade 1/2 (p